Current Pharmaceutical Biotechnology - Online First
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Towards Pharmaceutical Industry 5.0: Impact of Artificial Intelligence in Drug Discovery and Development
Available online: 03 November 2025More LessThe pharmaceutical industry is transforming with the advent of Industry 5.0, which is marked by integrating artificial intelligence (AI) into drug discovery and development. AI technologies, such as machine learning, deep learning, and natural language processing, revolutionize the traditional drug development pipeline by accelerating the identification of novel drug candidates, optimizing clinical trial designs, and personalizing therapies. Moreover, AI models enhance the prediction of drug efficacy, toxicity, and patient responses, minimizing the risk of failure of clinical trials. Nevertheless, despite these advancements, challenges remain in integrating AI into the pharmaceutical workflow, including data quality, regulatory concerns, and the need for interdisciplinary collaboration. This review explores the current state of AI applications in drug discovery, drug formulation and optimization, pharmacokinetics and pharmacodynamics, drug manufacturing and quality control, regulatory compliance and pharmacovigilance. Overall, AI is poised to redefine the landscape of drug discovery and development, fostering a new era of precision medicine and transforming patient outcomes globally, especially in the era of Industry 5.0.
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Ganoderma lucidum: A Medicinal Mushroom with Prebiotic and Anticancer Potential in Gastrointestinal Cancers
Authors: Akshay Shankar, Yashika Sharma, Mahak Rastogi, Rajkumar Tulsawani and Pramod KumarAvailable online: 28 October 2025More LessIntroductionGanoderma lucidum is considered a medicinal mushroom, as it primarily improves gut health by modulating the gut microbiota. As an abundant source of bioactive metabolites, antioxidants, and industrial enzymes, mushrooms make significant contributions to functional foods, nutrition, and pharmaceuticals. Polysaccharides derived from G. lucidum exhibit prebiotic potential, promoting the growth and activity of beneficial gut microorganisms.
MethodsThis systematic review examines the impact of white rot basidiomycetes metabolites on colorectal cancer treatment. We have compiled and analyzed data from PubMed, Google Scholar, and ResearchGate, presenting a comprehensive report with a table for clear understanding.
ResultsEvidence from in vivo and in vitro studies demonstrates that G. lucidum has potential as a gastrointestinal cancer inhibitor by inducing pro-apoptosis, autophagy, G0/G1 cell cycle arrest, and immunomodulation.
DiscussionBioactive metabolites and polysaccharides have prebiotic potential, enhancing the growth and activity of beneficial gut microorganisms that may lower the risk of gastrointestinal cancers by modifying gut bacteria. The prebiotic properties may boost immunity, reduce inflammation, and strengthen intestinal barrier integrity.
ConclusionThe current review explores the therapeutic potential of G. lucidum and other medicinal mushrooms as dietary supplements, focusing on their impact on the gut microbiome and gastrointestinal cancer.
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Identification of Potential Drug Targets for Generalized Anxiety Disorder: A Mendelian Randomization Study Based on Druggable Genes
Authors: Haining Zhang, Yusheng Li, Huanan Li, Shun Fan, Hongyi Wang, Jiacheng Zhang, Jingui Wang and An BaoAvailable online: 28 October 2025More LessIntroductionGeneralized anxiety disorder (GAD) is a prevalent and intricate mental disorder that significantly impairs the quality of life of patients. Currently, the exact etiology of GAD remains incompletely understood. Consequently, the discovery of novel drug targets for GAD is highly important.
MethodsWe obtained cis-eQTL data of druggable genes from the eQTLGen Consortium as the exposure data and GWAS data of GAD from the FinnGen Database as the outcome. The impact of druggable genes on GAD was simulated through Mendelian randomization analysis. Subsequently, a colocalization analysis was conducted to calculate the probability of shared pathogenic variants between the cis-eQTLs of druggable genes and GAD. To further validate our findings, a summary data-based Mendelian randomization (SMR) analysis was carried out.
ResultsMendelian randomization (MR) analysis identified 24 druggable genes with potential causal relationships, among which genetically predicted increased KDM5A levels were associated with a higher risk of GAD (OR=1.0991, 95% CI: 1.0021–1.2056, P=0.0451), suggesting a potential role of KDM5A gene expression in the pathogenesis of GAD. The GAD and KDM5A genes might share a causal variant. The SMR further verified the accuracy of the KDM5A gene.
DiscussionMR analysis identified KDM5A as a promising therapeutic target for GAD, with additional potential from genes, like MERTK and PPT1. However, the effectiveness of the relevant drug targets requires further validation.
ConclusionThis study suggested that the KDM5A gene might be a potential therapeutic target for treating GAD, providing a direction for future drug development in GAD patients.
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Flexible Pterostilbene Nanoliposomes for Enhanced Skin Delivery: Elasticity and Brightening Potential
Authors: Hong Meng, Jie Xiong, Wenxin Hu, Zhaohe Huang, Yifan He, Ze Zhang and Xiaojing PeiAvailable online: 21 October 2025More LessIntroductionThis study aimed to develop a local drug delivery system using pterostilbene (PTS) flexible nanoliposomes (FNL) to overcome its limitations, such as poor water solubility and instability under light and oxygen. The research focused on optimizing deformability and transdermal delivery using dipotassium glycyrrhizinate and a single-chain surfactant as membrane softeners.
MethodsThe encapsulation process and formulation of PTS FNL were systematically optimized through single-factor and orthogonal experiments. The physicochemical properties, stability, and transdermal performance of the optimized FNL were evaluated using dynamic light scattering, transmission electron microscopy (TEM), Turbiscan stability analysis, and in vitro/in vivo permeation studies.
ResultsThe optimized PTS FNL exhibited high encapsulation efficiency (96.49 ± 0.7%), a particle size of (60.11 ± 0.54 nm), PDI (0.237), a zeta potential of (-10.16 ± 0.54 mV), and good stability at 4°C and 25°C for three months. TEM confirmed spherical morphology, while in vitro studies demonstrated superior skin retention and prolonged permeation compared to PTS nanoliposomes (NL) and GTCC solutions. In vivo tests on human volunteers revealed that 0.4% PTS FNL cream significantly improved skin elasticity and chromaticity over 28 days without adverse effects.
DiscussionThe enhanced deformability of PTS FNL contributed to its improved transdermal delivery, making it a promising candidate for cosmetic applications. The study highlights the effectiveness of membrane softeners in optimizing liposomal formulations, though long-term stability under varied conditions warrants further investigation.
ConclusionThe developed PTS FNL system significantly enhances skin permeation and stability, demonstrating great potential for cosmetic use in anti-aging and skin-brightening formulations. This approach provides a viable strategy for improving the delivery of poorly soluble active ingredients.
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Technological Evolution and Hotspot Identification for Applying Artificial Intelligence in Pharmacy Based on Topic Modeling and Knowledge Graph
Authors: Zhijing Zhang, Ying Wang, Tong Wu, Baijun Liu, Yuhao Cui and Hongmei YuanAvailable online: 20 October 2025More LessIntroductionThe current pharmaceutical industry has increasingly adopted artificial intelligence (AI), integrating it across the entire industrial chain. While AI improves efficiency and reduces costs, it also faces challenges. This study explores both the technological evolution and contemporary innovation hotspots of AI in pharmacy.
MethodsThis study adopts a fusion analysis of multi-source data, constructing a bi-dimensional analytical framework based on patented inventions (1990-2024) and research articles (2020-2024) as research objects. The study applies the Latent Dirichlet Allocation (LDA) topic model to analyze the evolution of patent topics and employs CiteSpace to construct keyword knowledge graphs from research articles. By integrating patent and article data to define technical labels, the study identifies research hotspots from the perspective of the pharmaceutical life cycle, enabling cross-validation from both scientific and technical dimensions.
ResultsThe number of AI-related patents in the pharmaceutical field has grown rapidly over the past five years. Technological topics exhibit a distinct evolutionary trend. Research hotspots span the entire pharmaceutical life cycle, from drug development to clinical delivery. Additionally, potential directions for future technological development have been identified.
DiscussionResearch hotspots in the application of AI in pharmaceuticals include target identification, virtual screening, drug delivery, clinical trials, and pharmacovigilance. Precision medicine and explainable AI (XAI)-driven pharmacy modeling are expected to emerge as key directions for future technological development.
ConclusionAI has already reshaped the pharmaceutical industry through applications across all stages of the pharmaceutical life cycle. It is poised to attract growing research attention and drive innovative applications in the years ahead.
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Analysis of the Molecular Mechanism of Comorbidity Genes Between Breast Cancer and Depression
Authors: Hua Xie, Chenxiang Ding, Qianwen Li, Jie Xu, Wei Sheng, Renjian Feng and Huaidong ChengAvailable online: 17 October 2025More LessIntroductionBreast cancer and depression are both serious diseases that significantly impact women's physical health. The molecular mechanisms underlying their comorbidity remain elusive. This study aims to identify key genes and the molecular mechanisms associated with the comorbidity of breast cancer and depression using bioinformatics analysis methods.
MethodsData files for breast cancer and depression were obtained from the TCGA database and the NCBI GEO public database, respectively. The random survival forest algorithm was utilized to identify key genes co-expressed in both breast cancer and depression. Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) were employed to predict biological functions and signaling pathway differences influenced by these key genes in both diseases. The R package “RcisTarget” was utilized to predict molecular transcriptional regulatory relationships of the key genes. The CIBERSORT algorithm was applied for immune function correlation analysis of comorbid key genes. The differential expression of key genes was validated in breast cancer tissue and depression blood by qPCR.
ResultsThe TCGA database provided original mRNA expression data for breast cancer, while the NCBI GEO public database offered the dataset GSE58430 related to depression. Through functional enrichment and random survival forest analysis, CCNB1, MLPH, PSME1, and RACGAP1 were identified as four key genes. The specific signaling pathways、strong correlation with immune cells, and the potential molecular mechanisms of these four key genes were analyzed in breast cancer and depression. Their expression levels were verified in blood and tissue samples.
DiscussionThis study discovered the comorbidity genes of breast cancer and depression, providing a certain direction for the prevention and treatment of these two diseases. At present, breast cancer and depression are serious diseases that affect women's physical and mental health. The connection between the two is not very clear. This study proposes that these two diseases have comorbidity genes. The risk population of the disease can be detected early through testing, so as to intervene early and improve prognosis. However, the sample size of the database analyzed in this study was relatively small, and the sample size and methods for clinical validation were insufficient. Further in-depth research will be conducted in the future.
ConclusionThis study identified CCNB1, MLPH, PSME1, and RACGAP1 as key genes associated with the comorbidity of breast cancer and depression.
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Clinicopathological and Molecular Comparative Analysis of Hereditary vs. Sporadic Fumarate Hydratase-deficient Leiomyomatosis and Renal Carcinoma
Authors: Qi Chen, Pairidaguli Naibijiang, Yuanjing Hu, Qiuyue Du and Nuermaimaiti KuyaxikeziAvailable online: 17 October 2025More LessIntroductionFLRCC is a rare renal carcinoma subtype caused by FH mutations, categorized into hereditary (germline mutations) and sporadic (somatic mutations) forms. These forms are clinically and pathologically similar, complicating differentiation without genetic testing. The aim of this study is to investigate the clinicopathological and molecular genetic differences between hereditary and sporadic fumarate hydratase (FH)-deficient leiomyomatosis and renal cell carcinoma (FLRCC) to improve diagnostic accuracy and clinical management.
MethodA retrospective analysis of 14 FLRCC patients was conducted(May 2020-August 2023). Immunohistochemistry (FH, 2SC, p16), HE staining, and next-generation sequencing (NGS) of tumor tissues and blood leukocytes were performed.
ResultsThe 14 patients with FH-deficient leiomyoma were 25-54 years old, with a mean age of 36.21 ± 8.16. 78.5% (11/14) had clinical symptoms and multiple, large-sized fibroids (median maximum volume was 75 mm). Patients with leiomyoma and FH deficiency were divided into hereditary and sporadic FLRCC based on FH gene sequencing. Patients with HLRCC had an earlier onset, and the serum tumor marker CA125 was more significant. Moreover, tumor tissues from patients with hereditary and sporadic FH-deficient LRCC differed in immunohistochemical and HE staining characteristics, including more positive p16 and greater susceptibility to invasion and metastasis in patients with HLRCC, as well as malignant proliferation in patients with sporadic FH-deficient LRCC.
DiscussionAlthough limited by sample size, our preliminary findings indicated subtle differences in the age of onset, as well as immunohistochemical and histopathological features of hereditary and sporadic FH-deficient LRCC, facilitating the understanding and clinical diagnosis of FLRCC.
ConclusionIn clinical diagnosis, all information should be fully integrated, and a comprehensive judgment should be made to make a correct pathological diagnosis and provide targeted treatment for patients with an FH gene mutation.
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A Review on the Detection Methods of the Resistant Gene in Acinetobacter baumannii
Available online: 17 October 2025More LessThe rising prevalence of Multidrug-Resistant (MDR) Acinetobacter baumannii, particularly in hospital environments, has become a global health concern due to its capacity to cause severe infections and its resistance to conventional antibiotics. This article reviews the detection methods for the resistant genes, focusing on carbapenem-resistant A. baumannii (CRAB), where various phenotypic, molecular, and advanced diagnostic technologies, with particular attention to Fluorescence Resonance Energy Transfer (FRET) assays based on Quantum Dots (QDs) and Graphene Oxide (GO), are reviewed. These nanoparticle-based FRET assays show promising potential for rapid, sensitive, and multiplex detection of antibiotic resistance genes, offering significant improvements over traditional methods. In particular, integrating QDs and GO as donor-acceptor pairs in FRET allows real-time detection and high specificity of a key determinant of carbapenem resistance in A. baumannii. Adopting these advanced diagnostic tools could revolutionise infection control and management, providing timely and accurate diagnostics that are crucial in clinical settings.
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Lactate as a Metabolic Regulator in the Tumor Microenvironment: Linking Immunosuppression to Epigenetic Reprogramming
Authors: Weiwen Cheng, Pengwei Lai, Xinyuan Liu, Yihan Wang and Xiaohong DuAvailable online: 16 October 2025More LessA defining characteristic of tumor cells is their preferential reliance on aerobic glycolysis for lactate production, even under oxygen-sufficient conditions - the well-known Warburg effect. Recent advances have revealed lactate to be far more than a metabolic waste product, establishing its role as a versatile signaling molecule with multiple functions in cancer progression. Acting simultaneously as a pro-inflammatory mediator, hypoxia surrogate, tumor burden indicator, and metastasis predictor, lactate exerts profound and wide-ranging effects on immune cell function within the tumor microenvironment (TME).
The immunomodulatory properties of lactate create a profoundly immunosuppressive milieu that facilitates tumor immune evasion. It achieves this through coordinated suppression of antitumor immune effectors, including natural killer cells, dendritic cells, and cytotoxic T lymphocytes, while simultaneously enhancing the immunosuppressive functions of regulatory T cells, tumor-associated macrophages, and endothelial cells. This dual mechanism of action promotes tumor progression and metastasis through multiple pathways.
The groundbreaking discovery of lysine lactylation (Kla) has further expanded our understanding of lactate's biological roles, revealing a direct molecular connection between tumor metabolism and epigenetic regulation. This review provides a comprehensive synthesis of current knowledge regarding lactate-mediated immune modulation in the TME, examines recent advances in our understanding of lactate-dependent tumor biology, and evaluates emerging therapeutic strategies that target lactate metabolism. By integrating these perspectives, we aim to offer both fundamental insights and practical guidance for the development of novel anticancer therapies that target metabolic-epigenetic crosstalk.
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Exploring Niacinamide as a Multifunctional Agent for Skin Health and Rejuvenation
Authors: Khushi Kapoor, Sowmiya Shankar, Rukaiah Fatma Begum, Ankul Singh Suresh and Afreen NayeemAvailable online: 09 October 2025More LessNiacinamide, a water-soluble derivative of vitamin B3, has emerged as a versatile compound with wide-ranging therapeutic potential in dermatology. This review critically examines its formulation strategies, mechanisms of action, clinical benefits, safety profile, and advancements in delivery technologies. Niacinamide exhibits anti-inflammatory, antioxidant, and barrier-strengthening properties, making it valuable in the treatment of acne, rosacea, hyperpigmentation, and skin aging. It regulates sebum secretion, diminishes inflammatory lesions, supports collagen production, and protects against photoaging. Clinical studies affirm its effectiveness in enhancing skin tone, texture, and barrier integrity, with minimal adverse effects, even with prolonged use. Innovations in drug delivery, such as microencapsulation, liposomal carriers, and nanoparticle-based systems, have enhanced its dermal absorption and stability. Looking ahead, the integration of niacinamide into combination therapies and tailored skincare regimens offers promising opportunities to maximize its clinical utility. Overall, niacinamide stands out as a multifunctional dermatological agent with significant potential for promoting skin health and rejuvenation.
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Discoidin Domain Receptor 1 in Colonic Epithelial Cells: A Paracrine Driver of Colonic Fibrosis
Authors: Hang Gong, Xiao-Li Li, Yao-Hui Ma and De-Kui ZhangAvailable online: 08 October 2025More LessIntroductionThis study investigated the role and potential mechanisms of discoidin domain receptor 1 (DDR1) in colon fibrogenesis.
MethodsWe employed the DSS-induced chronic colitis and fibrosis model to evaluate the therapeutic potential of DDR1 knockout on colonic fibrosis. In vitro experiments involved generating human normal colonic epithelial cells (HIEC line) with DDR1 overexpression by lentivirus transfection. Human colonic fibroblasts were exposed to conditioned medium (CM) from the stably transfected cells that had been treated with transforming growth factor-beta 1 (TGF-β1). The cells were collected for molecular and biochemical analyses.
ResultsOur proteomics analysis of DDR1 indicated significant enrichment of proteins involved in the extracellular matrix and fibrosis. In DSS-treated DDR1-KO mice, attenuation of colonic fibrosis and reduced activation of colonic fibroblasts were observed, contrasting significantly with their counterparts in DSS-treated WT mice. Colonic fibroblasts exhibited a marked increase in α-smooth muscle actin and type I collagen expression when exposed to CM from HIEC cells with DDR1 overexpression. Finally, overexpression of DDR1 markedly elevated the levels of p-PI3K, p-Akt, p-mTOR, p62, and LC3B in HIEC cells, resulting in enhanced secretion of TGF-β1.
DiscussionDDR1 in HIEC cells attenuates autophagy primarily by activating the PI3K/AKT/ mTOR signaling axis and concurrently increasing the autophagic markers LC3B and p62, thereby inducing paracrine secretion of TGF-β1, which drives the activation and proliferation of colonic fibroblasts and elicits a robust profibrotic response.
ConclusionOur study suggests that DDR1 may be a potential therapeutic target for colonic fibrosis.
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Exploring the Interplay of PI3K/AKT/mTOR and JNK Signaling Pathways in Psoriasis: Insights from Systematic Review and Network Pharmacology Approach
Available online: 02 October 2025More LessIntroductionPsoriasis is a chronic inflammatory skin disease characterized by excessive keratinocyte proliferation, abnormal differentiation, and infiltration of inflammatory cells. Central to its pathogenesis are the PI3K/AKT/mTOR and JNK signaling pathways, which regulate inflammation and keratinocyte behavior.
MethodsThis study reviewed experimental data reported in the scientific literature and utilized network pharmacology to investigate the interplay between the PI3K/AKT/mTOR and JNK pathways, aiming to elucidate the underlying mechanisms of psoriasis. 709 records from Scopus, Web of Sciences, Cochrane Library and PubMed were reviewed without limitations until October 3, 2023. 85 articles were included in the systematic review.
ResultsKey molecules, including EGFR, Sortilin, and Cyr61, were identified as important links between these pathways, influencing cell survival and apoptosis. Flavonoids such as Rhododendrin, Erianin, and Fisetin were found to effectively target both of these pathways, potentially modifying cellular behavior and offering therapeutic benefits. The network analysis revealed that EGFR and AKT serve as critical connectors between hub genes CDC42 and GAPDH, with these flavonoids impacting downstream signaling molecules, including PI3K, AKT, mTOR, Grb2, JAK, STAT, Cyclooxygenase, HIF-1α, and MAPKs.
DiscussionThe findings highlight the pivotal role of the PI3K/AKT/mTOR pathway in promoting inflammation and cellular proliferation by activating NF-κB and HIF-1α.
ConclusionThis comprehensive review underscores the importance of the PI3K/AKT/mTOR and JNK pathways in understanding psoriasis mechanisms. Targeting these pathways with flavonoids may offer promising therapeutic strategies by modulating key molecular hubs involved in disease progression.
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Mechanistic Insights into the Therapeutic Role of Curcumin in Leukemia: Molecular Targets and Clinical Implications
Available online: 01 October 2025More LessLeukemia is one of the most widespread and life-threatening malignancies that originates in the blood and bone marrow. Despite advances in treatment, there remains a need for safer and more effective therapeutic agents with fewer side effects. This review investigates the therapeutic potential of curcumin (CUR), a naturally derived polyphenol, in leukemia management, with a focus on its molecular mechanisms and regulatory effects on various signaling pathways. Peer-reviewed publications were considered till March 2025. Various scientific databases, including PubMed, Scopus, Science Direct, SciFinder, Medline, and Google Scholar, were used to collect the literature knowledge. The review focuses on the role of curcumin in modulating key cellular processes, such as apoptosis, cell cycle arrest, and gene regulation, along with its interaction with several oncogenic and protective signaling cascades. Accordingly, CUR demonstrates potent antileukemic effects by promoting apoptosis and cell cycle arrest. It downregulates oncogenes, such as FLT3, Akt, ROS, and NF-κB, while protecting normal cells through upregulation of NRF-2, which enhances antioxidant production. Additionally, CUR modulates multiple signaling pathways, including NF-κB, JAK/STAT, PI3K/AKT, JNK/ERK, MAPK, Ras/Raf, and MMP, thereby affecting leukemia initiation, progression, and metastasis. CUR exhibits strong potential as a therapeutic agent for leukemia by targeting multiple molecular signaling pathways and promoting selective cytotoxicity against cancer cells. Further preclinical and clinical studies are necessary to validate its efficacy and overcome the limitations of the bioavailability parameters.
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The Contribution of Wearable Devices and Artificial Intelligence to Promoting Healthy Aging
Available online: 30 September 2025More LessIntroductionHealthy aging involves consistently maximizing opportunities to maintain and enhance physical and mental well-being, fostering independence, and sustaining a high quality of life. This review examines recent technological innovations aimed at promoting the well-being of older adults. The scope encompasses wearable devices and telemedicine, showcasing their potential to enhance the health and overall well-being of older individuals. The review highlights the crucial role of assistive technologies, including mobility aids, hearing aids, and adaptive home devices, in addressing the specific challenges associated with aging.
MethodsThe relevant literature was collected and selected based on the objective of the study and reviewed.
ResultsDigital technologies, including brain-computer interfaces (BCIs), are explored as potential solutions to enhance communication between healthcare providers and aging patients, considering engagement levels and active interaction. Sophisticated BCIs, such as electroencephalograms, electrocorticography, and signal modeling for real-time identification, play a crucial role in event detection, with machine learning algorithms enhancing signal processing for accurate decoding. The exploration of smart wearable systems for health monitoring emerges as a dynamic and promising field in the context of aging.
DiscussionFitbit® showcases accurate step counting, making it suitable for monitoring physical activity in older adults engaged in slow walking. ActiGraphÔ is evaluated for accuracy in monitoring physical activity in older adults, with results indicating reliable concurrence with Fitbit® devices. The study identifies several limitations, including sample size constraints, challenges in keeping pace with technological advancements, and the need for further investigation into the suitability of fitness trackers for individuals with significant mobility impairments.
ConclusionThe evolving landscape of wearable technologies, exemplified by Fitbit®, ActiGraphÔ, and other interventions, holds substantial promise for reshaping healthcare approaches for the aging population. Addressing the limitations will be crucial as research progresses to ensure the effective and ethical integration of wearables into geriatric care, maximizing their potential benefits.
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Evaluating the Protective Immunity of 5’-Cap Altered Rabies mRNA Vaccines in a Mouse Model
Authors: Teng Zhang and Wen ZhangAvailable online: 30 September 2025More LessIntroductionRabies Virus (RV or RABV) is a neurophilic pathogen predominantly transmitted to humans through bites, scratches, or wounds. Upon entering the central nervous system, the virus can cause severe symptoms, including acute encephalitis and paralysis, ultimately leading to death with an almost 100% mortality rate. Hence, it is essential to develop an effective oral rabies vaccine.
MethodsWe designed and synthesized three modified 5'-cap mRNA vaccines (RV-01(CAP-01), RV-01(CAP-02) and RV-01(CAP-03)) encoding rabies virus glycoproteins in vitro and evaluated their immunogenicity and protective effect in mice.
ResultsThe modified 5'-cap vaccine was successfully constructed and could be effectively expressed in HEK293 cells. The antibody detection results revealed the abundance of RABV-G in RV-01(CAP-01), RV-01(CAP-02) and RV-01(CAP-03). ELISPOT assays indicated that these variants promoted the production of immune-related cytokines. Furthermore, the modified 5'-cap vaccines could reduce the rabies viral load of mice and effectively prolong their survival.
DiscussionThe rabies mRNA vaccine had high efficacy and safety in preventing rabies, suggesting the great potential of mRNA as a promising candidate for RABV vaccines. However, the potential causes of the differences in the performance of the three modified 5'-cap rabies mRNA vaccines and the clinical application of 5’-Cap altered rabies mRNA vaccines need to be explored.
ConclusionHence, these results demonstrated that the modified 5’-cap mRNA vaccine was effective in inducing immune responses, which might be considered a promising prophylactic strategy for rabies.
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Pubescine as a Novel Antibacterial Agent Against Vancomycin-Resistant Enterococcus: Growth Inhibition, Antibiotic Synergy, and Anti-Biofilm Activity
By Raya SoltaneAvailable online: 26 September 2025More LessIntroductionThe rise of Vancomycin-Resistant Enterococcus (VRE) has become a major public health concern due to its resistance to conventional antibiotics and ability to form biofilms. The urgent need for novel therapeutic strategies has led to increased interest in natural compounds with antimicrobial potential. Pubescine (PBN), a steroidal alkaloid isolated from Holarrhena pubescens, has demonstrated antimicrobial properties, but its efficacy against VRE remains unexplored.
MethodsPBN was isolated and purified from Holarrhena pubescens using chromatographic techniques and identified through spectroscopic analysis. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were determined via broth microdilution assays. Time-kill assays assessed the bacteriostatic or bactericidal nature of PBN. Resistance development was evaluated through prolonged bacterial exposure to subinhibitory concentrations. Synergistic interactions with vancomycin and cefoxitin were analyzed using checkerboard microdilution assays. Biofilm formation and eradication were assessed via crystal violet staining and fluorescence imaging. Metabolic activity and oxidative stress induction were measured using the Alamar Blue assay and Reactive Oxygen Species (ROS) quantification, respectively.
ResultsPBN exhibited concentration-dependent inhibition of VRE growth, primarily exerting a bacteriostatic effect without promoting the development of resistance. Checkerboard assays revealed strong synergy between PBN and vancomycin (FICI = 0.1875) and cefoxitin (FICI = 0.3125), suggesting that PBN enhances the efficacy of these antibiotics.
DiscussionPBN significantly reduced biofilm formation and facilitated biofilm disruption at concentrations as low as 4 µg/mL. Metabolic assays demonstrated that PBN suppresses bacterial metabolic activity, while ROS quantification indicated a substantial increase in oxidative stress, suggesting a multi-targeted mechanism of action.
ConclusionThese findings establish PBN as a promising antimicrobial agent with potent activity against vancomycin-resistant Enterococcus faecalis. Its ability to enhance antibiotic efficacy, inhibit biofilm formation, and induce oxidative stress underscores its potential as a novel therapeutic strategy against multidrug-resistant infections. Further in vivo studies and pharmacokinetic evaluations are warranted to assess its clinical applicability.
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PhytoCAT: A Comprehensive Data Repository of PhytoChemicals for Affordable Breast Cancer Therapeutics
Available online: 26 September 2025More LessIntroductionBreast cancer is a global health challenge with a high mortality rate of 30% of total cases in a year. Breast cancer presents in 4 main types, namely, TNBC, HER2+, luminal A, and Luminal B. Current treatments, though not without side effects, incur substantial cost, and are rendered ineffective by rising drug resistance. Phytochemicals are being investigated for their beneficial effects on breast cancer. Systematically collecting, organizing, and analyzing this data from available literature could benefit the development of more potent chemopreventive and chemotherapeutic approaches with reduced side effects.
MethodsTo overcome the challenges posed by diverse naming practices, we adopted a sentiment (subjective) based text-mining approach to systematically extract and analyze data on anti-breast cancer phytochemicals from biomedical literature. This method is based on anchor and associated terms to capture authors’ sentiments regarding the therapeutic potential of these compounds. Subsequently, comprehensive and objective information was extracted and curated for each phytochemical, including target genes, pathways, study type, IC50 values, PMIDs, plant sources, and geographical availability.
ResultsPhytoCAT (PhytoChemical Affordable Therapeutics for Breast Cancer) is a comprehensive database of phytochemicals, plant extracts, and essential oils, enriched with links to phytogeographic data and chemical structures. PhytoCAT includes data on 28 essential oils, 470 plant extracts, and 1,649 phytochemical compounds. These compounds were classified into several chemical groups, including alkaloids (167), coumarins (43), flavonoids (290), lignans (47), quinones (43), saponins (27), sesquiterpenoid lactones (40), terpenoids (282), triterpenoid saponins (28), and xanthones (22) groups. Additionally, 505 phytochemicals belong to other subclasses such as esters, glucosides, phenanthrenes, and phenylpropanoids. Further, information on their mechanisms of action is also provided.
DiscussionPhytochemicals have gained significant attention in recent years because of their potential health benefits, particularly in the prevention and treatment of various diseases, including cancer. Compounds such as curcumin, resveratrol, and epigallocatechin gallate (EGCG) are examples of phytochemicals that have shown promise in preclinical studies. PhytoCAT offers a centralized and searchable database enriched with biological, chemical, and pharmacological details. Its structured presentation allows researchers to identify promising compounds and study patterns in chemical class-specific activity.
ConclusionPhytoCAT provides an evidence-based platform for researchers and clinicians to explore the potential of phytochemicals in breast cancer management. Although PhytoCAT has an advanced search engine, it lacks analytical tools, which we envisage integrating in the future. future. (https://phytocat.igib.res.in/)
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Understanding Antimicrobial Resistance: From Mechanisms to Public Health Implications
Available online: 12 September 2025More LessAntimicrobial resistance (AMR) is a global public health crisis driven by the overuse and misuse of antibiotics, inadequate infection control practices, and the evolution of microbes. It compromises the effective treatment of infections, posing severe implications for morbidity, mortality, and healthcare costs. Pathogens such as extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) exemplify the growing threat of drug-resistant organisms. This review provides an in-depth analysis of the mechanisms underlying AMR, including enzymatic drug inactivation, efflux pump overexpression, target site modification, and biofilm formation. Additionally, it examines the clinical and economic implications of AMR and assesses emerging strategies for mitigation. Innovative solutions, such as bacteriophage therapy, CRISPR-based genome editing, and the One Health approach, offer promising avenues to address resistance across the human, animal, and environmental health sectors. Coordinated global efforts in surveillance, stewardship, and research are essential to curbing the spread and impact of AMR.
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